Identification of a psoriasis susceptibility candidate gene by linkage disequilibrium mapping with a localized single nucleotide polymorphism map.


Journal Article

Psoriasis is a chronic inflammatory disease of the skin with both genetic and environmental risk factors. Here we describe the creation of a single-nucleotide polymorphism (SNP) map spanning 900-1200 kb of chromosome 3q21, which had been previously recognized as containing a psoriasis susceptibility locus, PSORS5. We genotyped 644 individuals, from 195 Swedish psoriatic families, for 19 polymorphisms. Linkage disequilibrium (LD) between marker and disease was assessed using the transmission/disequilibrium test (TDT). In the TDT analysis, alleles of three of these SNPs showed significant association with disease (P<0.05). A 160-kb interval encompassing these three SNPs was sequenced, and a coding sequence consisting of 13 exons was identified. The predicted protein shares 30-40% homology with the family of cation/chloride cotransporters. A five-marker haplotype spanning the 3' half of this gene is associated with psoriasis to a P value of 3.8<10(-5). We have called this gene SLC12A8, coding for a member of the solute carrier family 12 proteins. It belongs to a class of genes that were previously unrecognized as playing a role in psoriasis pathogenesis.

Full Text

Cited Authors

  • Hewett, D; Samuelsson, L; Polding, J; Enlund, F; Smart, D; Cantone, K; See, CG; Chadha, S; Inerot, A; Enerback, C; Montgomery, D; Christodolou, C; Robinson, P; Matthews, P; Plumpton, M; Wahlstrom, J; Swanbeck, G; Martinsson, T; Roses, A; Riley, J; Purvis, I

Published Date

  • March 2002

Published In

Volume / Issue

  • 79 / 3

Start / End Page

  • 305 - 314

PubMed ID

  • 11863360

Pubmed Central ID

  • 11863360

Electronic International Standard Serial Number (EISSN)

  • 1089-8646

International Standard Serial Number (ISSN)

  • 0888-7543

Digital Object Identifier (DOI)

  • 10.1006/geno.2002.6720


  • eng